Schaich 2021.

Study characteristics
General Information	Model names: CAIDE, FSRP, ASCVD‐PCE Type of study: external validation Aim of the study: to compare the CAIDE, FSRP, and ASCVD‐PCE risk scores in relation to future global cognitive performance, processing speed, working memory, and odds of global cognitive decline over 6 years in a multi‐ethnic population of middle‐aged and older adults in the USA Data source: Multi‐Ethnic Study of Atherosclerosis (MESA) Duration of follow‐up: mean 15.7 years (SD 0.7)
Participants	Country: USA Age: mean 60.1 years (SD 9.4) Sex: 53.3% women Inclusion criteria: no clinical cardiovascular disease at baseline Exclusion criteria: incomplete examinations; clinically recognised dementia at baseline
Predictors	Number of predictors: CAIDE: 8; FSRP: 9; ASCVD‐PCE: 9  Selection of predictors: based on the development study Definition of predictors: see Appendix 3
Outcomes	Type of outcome: secondary outcome  Definition and method of measurement: 3 standardised cognitive tests, namely Cognitive Abilities Screening Instrument (CASI, version 2; a measure of global cognitive performance), Digit Symbol Coding (DSC; a test of processing speed); and Digit Span (DS; a test of working memory)
Missing data	Number of participants with missing data: reported Handling of missing data: multiple imputation
Analysis	Number of participants: 4392 Number of events: 218 EPV: CAIDE: 27; FSRP: 24; ASCVD‐PCE: 24 Modelling method: logistic regression  Selection of predictors during modelling: based on the development study Performance measures:  Calibration: CAIDE: slope 1.05 (95% CI 0.71 to 1.40), intercept 0.04 (95% CI−0.18 to 0.10); FSRP: slope 1.05 (95% CI 0.77 to 1.34), intercept 0.04 (95% CI −0.19 to 0.10); ASCVD‐PCE: slope 1.05 (95% CI 0.78 to 1.33), intercept 0.03 (95% CI −0.17 to 0.12) Discrimination: CAIDE: C‐statistic [AUC] 0.632 (95% CI 0.596 to 0.669); FSRP: C‐statistic [AUC] 0.655(95% CI 0.615 to 0.693); ASCVD‐PCE: C‐statistic [AUC] 0.650 (95% CI 0.612 to 0.688)
PROBAST: applicability	Domain 1 (participant selection): low concern Domain 2 (predictors): low concern Domain 3 (outcome): low concern Overall applicability: low concern
Notes	Funding: "This work was supported by the National Institute on Ageing (grant numbers R03‐AG064569 to C.L.S.; P30‐AG049638 to S.C.; R01‐AG058969 and R01‐AG054069 to T.M.H.; P30‐AG059303 and K24‐AG045334 to J.A.L.; R01‐AG055606 to S.R.R.; and RF1‐AG054474 to J.D.) and the National Heart, Lung, and Blood Institute (grant numbers F32‐HL146075 to C.L.S. and R01‐HL127659 to S.R.H.). Multi‐Ethnic Study of Atherosclerosis is supported by the National Heart, Lung, and Blood Institute (contract numbers 75N92020D00001, HHSN268201500003I, N01‐HC‐95159, 75N92020D00005, N01‐HC‐95160, 75N92020D00002, N01‐HC‐95161, 75N92020D00003, N01‐HC‐95162, 75N92020D00006, N01‐HC‐95163, 75N92020D00004, N01‐HC‐95164, 75N92020D00007, N01‐HC‐95165, N01‐HC‐95166, N01‐HC‐95167, N01‐HC‐95168 and N01‐HC‐95169) and the National Center for Advancing Translational Sciences (grant numbers UL1‐TR‐000040, UL1‐TR‐001079, and UL1‐TR‐001420)." Conflicts of interest: "J.A.L. is a consultant to vTv Therapeutics and receives a stipend from Wolters Kluwer as Editor‐in‐Chief of the journal Alzheimer's Disease and Associated Disorders. Remaining authors declare no conflicts of interest."
Item	Authors' judgement	Support for judgement
Domain 1: Participant selection	No	Participants were free of clinical cardiovascular disease at baseline.
Domain 2: Predictors	Yes	Predictors were probably defined and assessed in the right way, and the predictors are available for when the model is put to use.
Domain 3: Outcome	Yes	Investigators used a suitably defined standard outcome without including any predictor information, determined the outcome similarly for the participants. They probably determined the outcome without knowledge of predictor data and following a reasonable time interval.
Domain 4: Analysis	Yes	Analysis is appropriate.
Overall judgement	No	≥ 1 domain at high risk.